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Protein

Hyaluronidase-4

Gene

HYAL4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Endo-hyaluronidase that degrades hyaluronan to smaller oligosaccharide fragments. Has also chondroitin sulfate hydrolase activity, The best substrate being the galactosaminidic linkage in the sequence of a trisulfated tetrasaccharide.2 Publications

Catalytic activityi

Random hydrolysis of (1->4)-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate.

pH dependencei

Optimum pH is 4.5-5 (for chondroitin sulfate hydrolase activity).1 Publication

Temperature dependencei

Optimum temperature is 37 degrees Celsius.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei147 – 1471Proton donorBy similarity

GO - Molecular functioni

  1. hyalurononglucosaminidase activity Source: ProtInc

GO - Biological processi

  1. carbohydrate metabolic process Source: InterPro
  2. chondroitin sulfate catabolic process Source: Ensembl
  3. glycosaminoglycan catabolic process Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Enzyme and pathway databases

BioCyciMetaCyc:HS02883-MONOMER.

Protein family/group databases

CAZyiGH56. Glycoside Hydrolase Family 56.

Names & Taxonomyi

Protein namesi
Recommended name:
Hyaluronidase-4 (EC:3.2.1.35)
Short name:
Hyal-4
Alternative name(s):
Chondroitin sulfate endo-beta-N-acetylgalactosaminidase
Chondroitin sulfate hydrolase
Short name:
CSHY
Hyaluronoglucosaminidase-4
Gene namesi
Name:HYAL4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:5323. HYAL4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 88CytoplasmicSequence Analysis
Transmembranei9 – 2921HelicalSequence AnalysisAdd
BLAST
Topological domaini30 – 453424ExtracellularSequence AnalysisAdd
BLAST
Transmembranei454 – 47421HelicalSequence AnalysisAdd
BLAST
Topological domaini475 – 4817CytoplasmicSequence Analysis

GO - Cellular componenti

  1. cell surface Source: Ensembl
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29574.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 481481Hyaluronidase-4PRO_0000301999Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi59 ↔ 351By similarity
Glycosylationi86 – 861N-linked (GlcNAc...)Sequence Analysis
Glycosylationi115 – 1151N-linked (GlcNAc...)Sequence Analysis
Glycosylationi177 – 1771N-linked (GlcNAc...) (complex)1 Publication
Disulfide bondi223 ↔ 237By similarity
Glycosylationi343 – 3431N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi376 ↔ 387By similarity
Disulfide bondi381 ↔ 435By similarity
Disulfide bondi437 ↔ 446By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ2M3T9.
PRIDEiQ2M3T9.

PTM databases

PhosphoSiteiQ2M3T9.

Expressioni

Tissue specificityi

Detected in placenta and skeletal muscle.1 Publication

Gene expression databases

BgeeiQ2M3T9.
CleanExiHS_HYAL4.
ExpressionAtlasiQ2M3T9. baseline.
GenevestigatoriQ2M3T9.

Organism-specific databases

HPAiHPA029453.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000223026.

Structurei

3D structure databases

ProteinModelPortaliQ2M3T9.
SMRiQ2M3T9. Positions 48-363.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glycosyl hydrolase 56 family.Curated

Keywords - Domaini

EGF-like domain, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG77606.
GeneTreeiENSGT00550000074476.
HOGENOMiHOG000015133.
HOVERGENiHBG052053.
InParanoidiQ2M3T9.
KOiK01197.
OMAiWNTKDVY.
PhylomeDBiQ2M3T9.
TreeFamiTF321598.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR000742. EG-like_dom.
IPR017853. Glycoside_hydrolase_SF.
IPR018155. Hyaluronidase.
[Graphical view]
PANTHERiPTHR11769. PTHR11769. 1 hit.
PfamiPF01630. Glyco_hydro_56. 1 hit.
[Graphical view]
PIRSFiPIRSF038193. Hyaluronidase. 1 hit.
PRINTSiPR00846. GLHYDRLASE56.
SMARTiSM00181. EGF. 1 hit.
[Graphical view]
SUPFAMiSSF51445. SSF51445. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q2M3T9-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MKVLSEGQLK LCVVQPVHLT SWLLIFFILK SISCLKPARL PIYQRKPFIA
60 70 80 90 100
AWNAPTDQCL IKYNLRLNLK MFPVIGSPLA KARGQNVTIF YVNRLGYYPW
110 120 130 140 150
YTSQGVPING GLPQNISLQV HLEKADQDIN YYIPAEDFSG LAVIDWEYWR
160 170 180 190 200
PQWARNWNSK DVYRQKSRKL ISDMGKNVSA TDIEYLAKVT FEESAKAFMK
210 220 230 240 250
ETIKLGIKSR PKGLWGYYLY PDCHNYNVYA PNYSGSCPED EVLRNNELSW
260 270 280 290 300
LWNSSAALYP SIGVWKSLGD SENILRFSKF RVHESMRIST MTSHDYALPV
310 320 330 340 350
FVYTRLGYRD EPLFFLSKQD LVSTIGESAA LGAAGIVIWG DMNLTASKAN
360 370 380 390 400
CTKVKQFVSS DLGSYIANVT RAAEVCSLHL CRNNGRCIRK MWNAPSYLHL
410 420 430 440 450
NPASYHIEAS EDGEFTVKGK ASDTDLAVMA DTFSCHCYQG YEGADCREIK
460 470 480
TADGCSGVSP SPGSLMTLCL LLLASYRSIQ L
Length:481
Mass (Da):54,249
Last modified:September 11, 2007 - v2
Checksum:i9D530009AA898D1F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti263 – 2631G → C in AAC98883. (PubMed:10493834)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti346 – 3461A → S.1 Publication
Corresponds to variant rs6949082 [ dbSNP | Ensembl ].
VAR_034936

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF009010 mRNA. Translation: AAC98883.1.
AB470346 mRNA. Translation: BAI49593.1.
AC006029 Genomic DNA. Translation: AAD43186.1.
CH236947 Genomic DNA. Translation: EAL24331.1.
CH471070 Genomic DNA. Translation: EAW83603.1.
BC104788 mRNA. Translation: AAI04789.1.
BC104790 mRNA. Translation: AAI04791.1.
CCDSiCCDS5789.1.
RefSeqiNP_036401.2. NM_012269.2.
XP_005250295.1. XM_005250238.1.
UniGeneiHs.28673.

Genome annotation databases

EnsembliENST00000223026; ENSP00000223026; ENSG00000106302.
ENST00000476325; ENSP00000417186; ENSG00000106302.
GeneIDi23553.
KEGGihsa:23553.
UCSCiuc003vlc.3. human.

Polymorphism databases

DMDMi158564281.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF009010 mRNA. Translation: AAC98883.1.
AB470346 mRNA. Translation: BAI49593.1.
AC006029 Genomic DNA. Translation: AAD43186.1.
CH236947 Genomic DNA. Translation: EAL24331.1.
CH471070 Genomic DNA. Translation: EAW83603.1.
BC104788 mRNA. Translation: AAI04789.1.
BC104790 mRNA. Translation: AAI04791.1.
CCDSiCCDS5789.1.
RefSeqiNP_036401.2. NM_012269.2.
XP_005250295.1. XM_005250238.1.
UniGeneiHs.28673.

3D structure databases

ProteinModelPortaliQ2M3T9.
SMRiQ2M3T9. Positions 48-363.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000223026.

Protein family/group databases

CAZyiGH56. Glycoside Hydrolase Family 56.

PTM databases

PhosphoSiteiQ2M3T9.

Polymorphism databases

DMDMi158564281.

Proteomic databases

PaxDbiQ2M3T9.
PRIDEiQ2M3T9.

Protocols and materials databases

DNASUi23553.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000223026; ENSP00000223026; ENSG00000106302.
ENST00000476325; ENSP00000417186; ENSG00000106302.
GeneIDi23553.
KEGGihsa:23553.
UCSCiuc003vlc.3. human.

Organism-specific databases

CTDi23553.
GeneCardsiGC07P123469.
H-InvDBHIX0033519.
HGNCiHGNC:5323. HYAL4.
HPAiHPA029453.
MIMi604510. gene.
neXtProtiNX_Q2M3T9.
PharmGKBiPA29574.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG77606.
GeneTreeiENSGT00550000074476.
HOGENOMiHOG000015133.
HOVERGENiHBG052053.
InParanoidiQ2M3T9.
KOiK01197.
OMAiWNTKDVY.
PhylomeDBiQ2M3T9.
TreeFamiTF321598.

Enzyme and pathway databases

BioCyciMetaCyc:HS02883-MONOMER.

Miscellaneous databases

GenomeRNAii23553.
NextBioi46112.
PROiQ2M3T9.
SOURCEiSearch...

Gene expression databases

BgeeiQ2M3T9.
CleanExiHS_HYAL4.
ExpressionAtlasiQ2M3T9. baseline.
GenevestigatoriQ2M3T9.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR000742. EG-like_dom.
IPR017853. Glycoside_hydrolase_SF.
IPR018155. Hyaluronidase.
[Graphical view]
PANTHERiPTHR11769. PTHR11769. 1 hit.
PfamiPF01630. Glyco_hydro_56. 1 hit.
[Graphical view]
PIRSFiPIRSF038193. Hyaluronidase. 1 hit.
PRINTSiPR00846. GLHYDRLASE56.
SMARTiSM00181. EGF. 1 hit.
[Graphical view]
SUPFAMiSSF51445. SSF51445. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Expression analysis of six paralogous human hyaluronidase genes clustered on chromosomes 3p21 and 7q31."
    Csoka A.B., Scherer S.W., Stern R.
    Genomics 60:356-361(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
  2. "Identification of human hyaluronidase-4 as a novel chondroitin sulfate hydrolase that preferentially cleaves the galactosaminidic linkage in the trisulfated tetrasaccharide sequence."
    Kaneiwa T., Mizumoto S., Sugahara K., Yamada S.
    Glycobiology 20:300-309(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
  3. "The DNA sequence of human chromosome 7."
    Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
    , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
    Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "Human chromosome 7: DNA sequence and biology."
    Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
    , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
    Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-346.
    Tissue: Cerebellum.
  7. "Structures of vertebrate hyaluronidases and their unique enzymatic mechanism of hydrolysis."
    Jedrzejas M.J., Stern R.
    Proteins 61:227-238(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, 3D-STRUCTURE MODELING.
  8. Cited for: GLYCOSYLATION AT ASN-177.

Entry informationi

Entry nameiHYAL4_HUMAN
AccessioniPrimary (citable) accession number: Q2M3T9
Secondary accession number(s): D0VXG1, Q9UL99, Q9Y6T9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: September 11, 2007
Last modified: January 7, 2015
This is version 82 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.